The present invention relates generally to the medical arts.
Arterial circulation disorders, such as peripheral arterial occlusive disease, acute cerebral insult, ocular infarct, hearing loss, placental circulation disorders, etc., are among frequently occurring diseases, which sometimes require extremely lengthy treatment (with varied success) and present significant impairment.
Hydroxyethyl starch (HES) has already been used within the framework of hemodilution therapy in patients with arterial circulation disorders. The therapeutic principle in hemodilution is the rheologic improvement of the blood, such as lowering the hematocrit, reducing plasma viscosity, as well as normalizing erythrocyte aggregation. Hematocrit, plasma viscosity, and erythrocyte aggregation are rheologic parameters whose value provides indications concerning the fluidity of the blood see Kiesewetter, VASOMED, Vol. 4, 10/92, pp. 672-686!.
In clinical studies the principle of action was confirmed, whereby the clinical relevance of improved rheology, for example, in peripheral arterial occlusive disease was demonstrated in an increase in pain-free walking distance or in acute cerebral infarct in an improvement in neurological scores.
Currently, commercial medium-molecular hydroxyethyl starch, such as HES 200/0.60 to 0.66 and HES 200/0.5 are used in hemodilution therapy for circulation disorders. In hemodilution therapy with HES solutions, large quantities of these solutions are infused, e.g., as much as 10 l of a 10% HES solution within a period of 10 days with acute cerebral infarct and up to 42 days with peripheral arterial occlusive disease, which corresponds to an infused quantity of 1 kg of HES. In examinations, it has been determined that multiple infusions of HES solutions resulted in cumulation of the serum HES concentrations. Thus, for example, with repeated administration of HES 450/0.7 (2.times.weekly 500 ml 6% HES solution over a period of 6 weeks) serum concentrations around 20 g/l were obtained, and 16 weeks after this repeated administration HES concentrations of approximately 1.32 g/l were still found FORTSCHRITTE DER MEDIZIN Vol. 97, No. 40 (1979), pp. 1809-1813!.
Furthermore, with the infusion of the prior art HES solutions, because of the cumulation of the serum HES concentrations, adverse effects, such as allergic reactions (e.g., pruritus, etc.), were observed. To avoid such adverse effects, specialists recommended that in therapy with HES patients be infused with no more than 150 g hydroxyethyl starch, which corresponds to 3.times.500 ml HES 200/0.5 (10%) or 5.times.500 ml HES 200/0.5 (6%) per week J. Koscielny, H. Kiesewetter, et al., Hemodilution, Springer Verlag, 1991, p. 214!.
For microcirculation, improvement of which is an essential principle or the most essential principle in the therapy of peripheral circulation disorders, plasma viscosity is an important criterion along with hematocrit and erythrocyte aggregation. Whereas previously used HES solutions lower the hematocrit value and improve erythrocyte aggregation, their effect on the lowering of plasma viscosity to bring about a significant improvement of microcirculation was inadequate. Thus, for the treatment of peripheral arterial occlusive diseases, HES is often combined with vasoactive substances.
With regard to these disadvantages, there continues to be a need for suitable agents for improvement of microcirculation in peripheral circulation disorders, such as peripheral arterial occlusive diseases, which do not have the disadvantages of the prior art agents.
The object of the present invention is thus to provide an agent for improvement of microcirculation in peripheral circulation disorders, in particular in peripheral arterial occlusive diseases in Stage II according to Fontaine, with which microcirculation can be substantially improved, even without the addition of vasoactive substances.